We propose the use of nanotechnology approaches for controlling interfaces between Temporomandibular Joint (TMJ) implants and the surrounding tissues. It is estimated that more than 10 million people suffer from the TMJ-related disorder symptoms in the Unites States with a clinical need for TMJ implant designs that will show propensity for osseointegration. We propose the use of nanostructured functionally graded metalloceramic coatings for articulating surfaces and nanostructured hydroxyapatitecoated fixation screws for the TMJ implants. The four specific aims are: (1) development of nanotechnology tools and methods for deposition of metalloceramic coatings having a gradual structural transition from the coating/implant interface (metallic bonding) to the outer implant surface (nanometer-level smooth ceramic) (2) development of nanostructured hydroxyapatite coatings on fixation screws to withstand the shear stresses during insertion of the implants and surface functionalization for osseointegration of the TMJ implant (3) In vitro investigations to compare the adhesion and osteoblastic differentiation of mesenchymal cells (MSC's) on the nanostructured coatings. Test the ability of these coatings to adsorb pro-adhesive proteins from blood, and determine whether functionalizing the surface via application of a synthetic pro-adhesive peptide (RGD) enhances MSC adhesion and differentiation, relative to uncoated materials with adsorbed serum proteins and (4) In vivo investigations to characterize the short term (initial organic and cellular responses) and long term (soft tissue and bone integration) responses of control and proposed biomaterials with and without functionalized surfaces specific to overall biointegration and biocompatibility profiles. [unreadable] A multidisciplinary research team consisting of physicists, a biomedical engineer, a cell biologist, and a biomaterials and dental surgeon has been assembled to address TMJ osseointegration. The primary focus is to improve the fixation, wear resistance and osseointegration for long-term success of TMJ implants and lower the need for multiple or revision surgeries. The novel nanostructured functionally graded surface architectures validated by our in vitro and in vivo studies will have a broader impact on a variety of other metal-on-metal and metal-on-polyethylene implants currently in clinical use. [unreadable] [unreadable]